PROJECT SUMMARY/ABSTRACT This application is a shared instrumentation grant from the Analytical Imaging Facility (AIF) at the Albert Einstein College of Medicine to acquire a new, advanced point-scanning confocal microscope. The AIF supports NIH-funded investigators by giving them access to state-of-the- art microscopy technologies that enhance cutting edge, collaborative, and multidisciplinary research. Currently, the AIF has several confocal microscopes available: two point-scanning confocals, a spinning disk confocal and a line scanning confocal. However, three out of the four existing confocal microscopes are reaching their end of usage due to aging, discontinuation of service contracts by the vendors, and difficulties obtaining parts needed for repair. The one remaining point-scanning confocal microscope will not be able to support the 70+ labs currently using confocal technology at Einstein. In order to continue to support the ongoing NIH funded biomedical research that relies on confocal microscopy, we need to replace the failing instruments with one new confocal microscope that can offer all the functions of our current microscopes, including regular multi-channel high resolution 3D imaging, live-cell imaging at fast frame rates, and flexibility in channel set-up to enable use of many different fluorophores. In addition, since the acquisition of our last confocal in 2007, there have been some major innovations in the field of confocal microscopy with regard to detectors, laser design and acquisition speed, and we believe that an update in technology will enable some of our NIH- funded researchers to conduct experiments that have previously been challenging to conduct. Overall, acquisition of this advanced instrument will have a high impact on the NIH-funded biomedical research at Einstein, including the following major user projects: studies of the developmental biology and genetics of Drosophila (Dr. Baker), studies of central inflammatory regulation of systemic aging in humans (Dr. Cai), studies of cancer metastasis, invasion and intravasation (Dr. Condeelis), mitochondrial function and mitophagy (Dr. Kitsis), the regulation of autophagy and programmed cell death in the context of diabetes (Dr. Pessin), mechanisms of mRNA regulation in primary hippocampal neurons and tissues (Dr. Singer) and investigation of gap junction structural dynamics in the brain and bone (Dr. Spray). There are also additional minor user projects and 70+ labs currently using confocal microscopy here at Einstein that will benefit from this technology.